Clinical Features of Germline Variations in Breast Cancer Patients Revealed by BRCA1 and BRCA2 Genes Using Next Generation Sequencing

Abstract Background. Breast cancer is among the most common female cancers worldwide according to WHO 2020 data. Breast cancer tumor suppressor genes (BRCA1 and BRCA2) are the most susceptibility genes for breast cancer. Thus, authors aimed to detect germline mutations of BRCA1 and BRCA2 genes among Egyptian female breast cancer patients. Methods. Blood samples were collected from primary breast cancer patients (n=22), benign breast lesions (n=5) and healthy control (n=7). Then DNA was extracted and germline mutational profiling of BRCA1 and BRCA2 were studied using next generation sequencer (Ion Torrent personal Genome Machine [PGM]).Results. A total of 135 genetic variations were detected, 59 in BRCA1 and 76 BRCA2, 2indels and 133 SNV, nearly 55% of those variants were missense variants, 38% were synonyms and 7% were nonsense. Ten exonic and 49 intronic variations were detected in BRCA1. The exonic variants in BRCA1were grouped as 6 ​​synonymous variants, one 3-prime UTR variant, 12 missense variants, 11 non coding transcript exon variants, 2 splice_region_variant,synonymous_variant, and 2 stop gain variants were previously reported to be pathogenic in Clinvar database. For BRCA2, 55 intronic variations and 21 exonic variants were detected, from the exonic variations there were 13 new mutations and 8 previously reported (7 were benign and only one were reported to be with conflicting pathogenicity on the clinvar database). Conclusion. This study reports gremline profiling of BRCA1 and BRCA2genetic mutations among Egyptian females with breast cancer using next generation sequencing as high throughput technology for a better coverage for mutational analysis that may benefit in clinical routine practice.